Allergy Asthma Respir Dis AARD Allergy, Asthma & Respiratory Disease 2288-0402 2288-0410 The Korean Academy of Pediatric Allergy and Respiratory Disease; The Korean Academy of Asthma, Allergy and Clinical Immunology 10.4168/aard.2014.2.4.285 Original Article Suppressive effects of long-term treatment with inhaled steroids on hypothalamic-pituitary-adrenal axis in asthma Sim Da Woon Choi Inseon S. Kim Seung-Hun Department of Allergy, Chonnam National University Medical School, Gwangju, Korea. Correspondence to: Inseon S. Choi. Department of Allergy, Chonnam National University Hospital, Chonnam National University Medical School, 42 Jebong-ro, Dong-gu, Gwangju 501-757, Korea. Tel: +82-62-220-6571, Fax: +82-62-225-8578, ischoi@chonnam.ac.kr 09 2014 30 09 2014 2 4 285 292 22 01 2014 29 05 2014 02 06 2014 © 2014 The Korean Academy of Pediatric Allergy and Respiratory Disease; The Korean Academy of Asthma, Allergy and Clinical Immunology 2014 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/). Purpose

Long-term treatment with inhaled steroids (ICS), especially fluticasone that developed lately, may suppress the hypothalamic-pituitary-adrenal (HPA) axis. This study investigated the relationship between ICS use and HPA axis suppression in asthmatics under ICS treatment for average 4.5 years.

 Methods

The medical records of 129 adult asthmatics who received ICS treatment for 6 months or more and underwent a corticotropin stimulation test from January 2005 to August 2013 were retrospectively reviewed.

 Results

The patients received ICS only (n=87) were found to have an abnormal response to the corticotropin test in as high as 32.2%, and those received ICS in combination with oral steroids (n=42) had a significantly higher prevalence of the response (71.4%, P<0.001). Abnormal responses to corticotropin occurred depending on ICS daily doses (low, n=8, 12.5%; medium, n=19, 36.8%; high, n=102, 49.0%; χ2=4.384, P=0.036). Among the subjects received ICS only, nasal steroid doses (P=0.016) but not ICS doses (P=0.159) were significantly higher in those with abnormal responses than the others. Among all the subjects, oral steroid use (odds ratio [OR], 4.27; 95% confidence interval [CI], 2.35-11.80; P<0.001) and nasal steroid dose (OR, 1.02; 95% CI, 1.00-1.04; P=0.015) were significant risk factors for HPA axis suppression.

 Conclusion

One-third of asthmatics under long-term treatment with ICS showed a suppression of the HPA axis in a dose-dependent manner. Oral or nasal steroid use may be a risk factor for the suppression. However, since our results may have been overestimated due to subject selection bias, further prospective case-control studies are warranted.

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Comparison of adrenal suppression markers (morning cortisol ≤3 µg/dL [A], serum cortisol <18 µg/dL before and 60 minutes after administration of 250-µg ACTH [B], and adrenal insufficiency determined by abnormal ACTH test response or morning cortisol ≤3 µg/dL [C]) between asthma patients used inhaled steroid (ICS) only and those used inhaled +oral steroids (OCS). ACTH, adrenocorticotrophic hormone.

Comparison of adrenal suppression markers (morning cortisol ≤3µg/dL [A], serum cortisol <18 µg/dL before and 60 minutes after administration of 250-µg ACTH [B], and adrenal insufficiency determined by abnormal ACTH test response or morning cortisol ≤3 µg/dL [C]) among asthma patient groups classified according to the daily doses of inhaled steroids. ACTH, adrenocorticotrophic hormone.

Correlation between serum cortisol levels at 60 minutes after administration of 250-µg adrenocorticotrophic hormone (ACTH) and oral (A), nasal (B), or inhaled steroid doses (C).

The demographics and clinical characteristics of asthma patients treated with inhaled corticosteroid and classified according to the daily doses of inhaled steroids

Values are presented as mean±standard deviation or number (%).

ICS, inhaled corticosteroid; FEV1, forced expiratory volume in one second; ACTH, adrenocorticotrophic hormone.

*Abnormal ACTH response: serum cortisol <18 µg/dL before and 60 minutes after administration of 250-µg adrenocorticotrophic hormone. †Adrenal insufficiency: abnormal ACTH response or morning cortisol ≤3 µg/dL.

The demographics and clinical characteristics of asthma patients used inhaled corticosteroid only and classified according to the response to a 250-µg ACTH stimulation test*

Values are presented as mean±standard deviation or number (%).

ACTH, adrenocorticotrophic hormone; ICS, inhaled corticosteroid; FEV1, forced expiratory volume in one second.

*Abnormal ACTH stimulation test: serum cortisol<18 µg/dL before or 60 minutes after administration of 250-µg ACTH.

Relative risk for hypothalamic-pituitary-adrenal axis suppression determined by response to 250-µg ACTH stimulation in patients with asthma

ACTH, adrenocorticotrophic hormone; OR, odds ratio; CI, confidence interval.

*Compared to low/medium dose inhaled steroid.